Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas

Szabó, Balázs; Nelhűbel, Györgyi A.; Kárpáti, Adél; Kenessey, István; Jóri, Balázs; Székely, Csilla; Peták, István; Lotz, Gábor; Hegedüs, Zita; Hegedűs, Balázs; Füle, Tibor; Döme, Balázs; Tı́már, József; Tóvári, József

doi:10.1016/j.oraloncology.2011.03.020

Cited by 76 publications

(64 citation statements)

References 36 publications

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“…Overexpression of epidermal growth factor receptor (EGFR) can be detected in more than 80-90 % of HNSCC [32] either with or without gene amplification, and have been shown as a marker of poor prognosis [33,34]. In our cohort, EGFR levels showed regional preference in HNSCC with the highest EGFR expression in oral cancers and the lowest in glottic cancers.…”

Section: Discussionmentioning

confidence: 77%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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Head and neck squamous cell carcinomas (HNSC C) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16 ink4 and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16 ink4

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Section: Discussionmentioning

confidence: 77%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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“…This may be attributable to higher EGFR copy number in HPV-negative compared with HPV-positive tumors [33][34][35][36]. EGFR signaling results in activation of several downstream pathways that may affect transcription or translation of VEGF, including the Ras/MAPK, PI3 K/ Akt/mTOR, and STAT3 pathways [37,38].…”

Section: Discussionmentioning

confidence: 99%

“…This search yielded 322 eligible cases. Among these cases, we identified 103 with tumor HPV status recorded in the pathology report, as determined by in situ hybridization (ISH) using a probe cocktail for HPV types 6,11,16,18,31,33,35,45, 51, and 52 (Dako #Y1404). Formalin-fixed, paraffin-embedded tumors were requested from storage for these 103 cases, and tumor blocks were retrieved for 71.…”

Section: Study Populationmentioning

confidence: 99%

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

Troy

Weissfeld

Youk

et al. 2013

Head and Neck Pathol

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There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal-Wallis tests were used to compare staining scores (intensity 9 percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (q) in all cases, and stratified by HPV status.

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“…In the observations of Gao et al, EGFR overexpression was associated with poor survival in HNSCC patients receiving CCRT (19). Szabó et al examined expression and genetic alteration of EGFR gene by FISH with 71 HNSCC patients and observed that increased copy number and overexpression of the EGFR gene was associated with poor prognosis in HNSCC (20). However, neither group examined the CNAs involving the responsiveness to CCRT in terms of recurrence.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer

et al. 2016

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Abstract. Although concomitant chemoradiotherapy (CCRT)has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT-related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome-wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray-comparative genomic hybridization and candidate CNAs were validated by quantitative RT-PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT-failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease-specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT-failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT-failure.

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Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas

Cited by 76 publications

References 36 publications

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer

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